93 research outputs found
Prevalence and Subtypes of Mild Cognitive Impairment in Parkinson's Disease.
The current study examined the prevalence and subtypes of Mild Cognitive Impairment (MCI) in an Australian sample of people with Parkinson's Disease (PD). Seventy participants with PD completed neuropsychological assessments of their cognitive performance, using MDS Task Force Level II diagnostic criteria for PD-MCI. A cut-off score of less than one standard deviation (SD) below normative data determined impaired performance on a neuropsychological test. Of 70 participants, 45 (64%) met Level II diagnostic criteria for PD-MCI. Among those with PD-MCI, 42 (93%) were identified as having multiple domain impairment (28 as amnestic multiple domain and 14 as nonamnestic multiple domain). Single domain impairment was less frequent (2 amnestic/1 nonamnestic). Significant differences were found between the PD-MCI and Normal Cognition groups, across all cognitive domains. Multiple domain cognitive impairment was more frequent than single domain impairment in an Australian sample of people with PD. However, PD-MCI is heterogeneous and current prevalence and subtyping statistics may be an artifact of variable application methods of the criteria (e.g., cut off scores and number of tests). Future longitudinal studies refining the criteria will assist with subtyping the progression of PD-MCI, while identifying individuals who may benefit from pharmacological and nonpharmacological interventions
ΠΠ΅ΡΠΎΠ΄ΠΎΠ»ΠΎΠ³ΠΈΡ ΡΠΈΠ½ΡΠ΅Π·Π° Π°ΡΡ ΠΈΡΠ΅ΠΊΡΡΡΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΠ½ΠΎ-ΡΠ΅Ρ Π½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° Π°Π²ΡΠΎΠΌΠ°ΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° ΠΎΠ±ΡΡΠ°Π½ΠΎΠ²ΠΊΠΈ
ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΊ ΠΏΡΠΎΠ΅ΠΊΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π°ΡΡ
ΠΈΡΠ΅ΠΊΡΡΡΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΠ½ΠΎ-ΡΠ΅Ρ
Π½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° Π°Π²ΡΠΎΠΌΠ°ΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³Π° ΠΎΠ±ΡΡΠ°Π½ΠΎΠ²ΠΊΠΈ Π² ΡΠ΅Π°Π»ΡΠ½ΠΎΠΌ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ, ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΡΠΉ Π½Π° ΠΊΠ»Π°ΡΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΠ΅ΡΠ°Π΅ΠΌΡΡ
ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
Π·Π°Π΄Π°Ρ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΊΠ»Π°ΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΈ Π²ΡΠ±ΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π° ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² ΠΏΠΎΠ΄ΠΎΠ±ΠΈΡ. Π Π°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΠΉ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΈΠ· ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π° ΡΡΠ½ΠΊΡΠΈΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Π²ΡΠ΄Π΅Π»ΠΈΡΡ ΠΏΠΎΠ΄ΠΎΠ±Π½ΡΠ΅ (ΠΏΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΡΠΌ ΠΏΡΠΈΠ·Π½Π°ΠΊΠ°ΠΌ) ΠΈ ΠΎΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ ΠΈΡ
Π² Π°ΡΡ
ΠΈΡΠ΅ΠΊΡΡΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΡ (ΡΠ½ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠ΅ ΠΌΠΎΠ΄ΡΠ»ΠΈ).ΠΠ°ΠΏΡΠΎΠΏΠΎΠ½ΠΎΠ²Π°Π½ΠΎ ΠΏΡΠ΄Ρ
ΡΠ΄ Π΄ΠΎ ΠΏΡΠΎΠ΅ΠΊΡΡΠ²Π°Π½Π½Ρ Π°ΡΡ
ΡΡΠ΅ΠΊΡΡΡΠΈ ΡΠ΅Π½ΡΡΡ ΠΎΠ±ΡΠΎΠ±ΠΊΠΈ ΡΠ½ΡΠΎΡΠΌΠ°ΡΡΡ Π°Π²ΡΠΎΠΌΠ°ΡΠΈΠ·ΠΎΠ²Π°Π½ΠΎΡ ΡΠΈΡΡΠ΅ΠΌΠΈ ΠΌΠΎΠ½ΡΡΠΎΡΠΈΠ½Π³Ρ ΡΠ΅ΡΠ΅Π΄ΠΎΠ²ΠΈΡΠ° Π² ΡΠ΅Π°Π»ΡΠ½ΠΎΠΌΡ ΡΠ°ΡΡ, ΡΠΎ Π·Π°ΡΠ½ΠΎΠ²Π°Π½ΠΈΠΉ Π½Π° ΠΊΠ»Π°ΡΠΈΡΡΠΊΠ°ΡΡΡ ΡΡΠ½ΠΊΡΡΠΎΠ½Π°Π»ΡΠ½ΠΈΡ
Π·Π°Π΄Π°Ρ Π½Π° ΠΏΡΠ΄ΡΡΠ°Π²Ρ ΠΌΠ΅ΡΠΎΠ΄ΡΠ² ΠΊΠ»Π°ΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΡΠ·Ρ Ρ ΠΎΠ±ΡΠ°Π½ΠΎΡ ΠΌΠ½ΠΎΠΆΠΈΠ½ΠΈ ΠΎΠ·Π½Π°ΠΊ ΡΡ
ΠΎΠΆΠΎΡΡΡ. Π ΠΎΠ·ΡΠΎΠ±Π»Π΅Π½ΠΈΠΉ ΠΏΡΠ΄Ρ
ΡΠ΄ Π΄ΠΎΠ·Π²ΠΎΠ»ΡΡ Π²ΠΈΠ±ΡΠ°ΡΠΈ ΡΠ· ΠΌΠ½ΠΎΠΆΠΈΠ½ΠΈ ΡΡΠ½ΠΊΡΡΠΉ ΡΠΈΡΡΠ΅ΠΌΠΈ ΡΡ
ΠΎΠΆΡ (Π·Π° ΠΏΠ΅Π²Π½ΠΈΠΌΠΈ ΠΎΠ·Π½Π°ΠΊΠ°ΠΌΠΈ) Ρ ΠΏΠΎΡΠ΄Π½Π°ΡΠΈ ΡΡ
Π² Π°ΡΡ
ΡΡΠ΅ΠΊΡΡΡΠ½Ρ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΈ (ΡΠ½ΡΡΡΠΊΠΎΠ²Π°Π½Ρ ΡΡΠ½ΠΊΡΡΠΎΠ½Π°Π»ΡΠ½Ρ ΠΌΠΎΠ΄ΡΠ»Ρ).The approach to designing architecture of the information processing complex of the automated real time conditions monitoring system based on classification of functional tasks on the basis of methods of cluster analysis and the chosen set of similarity attributes is offered. The developed approach allows to allocate from a set of functions the systems similar (on certain attributes) and to unite them in architectural components (unified functional modules)
The RAB39B p.G192R mutation causes X-linked dominant Parkinsonβs disease
Objective: To identify the causal gene in a multi-incident U.S. kindred with Parkinsonβs disease (PD). Methods: We characterized a family with a classical PD phenotype in which 7 individuals (5 males and 2 females) were affected with a mean age at onset of 46.1 years (range, 29-57 years). We performed whole exome sequencing on 4 affected and 1 unaffected family members. Sanger-sequencing was then used to verify and genotype all candidate variants in the remainder of the pedigree. Cultured cells transfected with wild-type or mutant constructs were used to characterize proteins of interest. Results: We identified a missense mutation (c.574G > A; p.G192R) in the RAB39B gene that closely segregated with disease and exhibited X-linked dominant inheritance with reduced penetrance in females. The mutation occurred in a highly conserved amino acid residue and was not observed among 87,725 X chromosomes in the Exome Aggregation Consortium dataset. Sequencing of the RAB39B coding region in 587 familial PD cases yielded two additional mutations (c.428C > G [p.A143G] and c.624_626delGAG [p.R209del]) that were predicted to be deleterious in silico but occurred in families that were not sufficiently informative to assess segregation with disease. Experiments in PC12 and SK-N-BE(2)C cells demonstrated that p.G192R resulted in mislocalization of the mutant protein, possibly by altering the structure of the hypervariable C-terminal domain which mediates intracellular targeting. Conclusions: Our findings implicate RAB39B, an essential regulator of vesicular-trafficking, in clinically typical PD. Further characterization of normal and aberrant RAB39B function might elucidate important mechanisms underlying neurodegeneration in PD and related disorders. Electronic supplementary material The online version of this article (doi:10.1186/s13024-015-0045-4) contains supplementary material, which is available to authorized users
Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression
Variation in the CYP3A enzymes, which act in drug metabolism, influences circulating steroid levels and responses to half of all oxidatively metabolized drugs. CYP3A activity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically expressed at high levels in a minority of Americans of European descent and Europeans (hereafter collectively referred to as 'Caucasians'). Only people with at least one CYP3A5*1 allele express large amounts of CYP3A5. Our findings show that single-nucleotide polymorphisms (SNPs) in CYP3A5*3 and CYP3A5*6 that cause alternative splicing and protein truncation result in the absence of CYP3A5 from tissues of some people. CYP3A5 was more frequently expressed in livers of African Americans (60%) than in those of Caucasians (33%). Because CYP3A5 represents at least 50% of the total hepatic CYP3A content in people polymorphically expressing CYP3A5, CYP3A5 may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines
Genetic basis of a cognitive complexity metric
Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the molecular level, we found preliminary support for four single-marker loci (one in the gene DGKB), and at a gene-based level for the NPS gene, having influence on cognition. These results indicate that genetic sources influencing relational processing are a key component of the genetic architecture of broader cognitive abilities. Further, they suggest a genetic cascade, whereby genetic factors influencing capacity limitation in relational processing have a flow-on effect to more complex cognitive traits, including reasoning and working memory, and ultimately, IQ
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